Pyridyl-1, 3, 5-oxathiazolinones and process for their production



United States Patent 3,258,464 PYRIDYL-l,3,5-OXATHIAZOLINONES ANDPROCESS FOR THEIR PRODUCTION Klaus Sasse, Cologne-Stammheim, and MariaBriimmelhues, Wuppertal-Sonnborn, Germany, assignors to FarbcnfabrikenBayer Aktiengesellschaft, Leverlrusen,

Germany, a German corporation No Drawing. Filed Oct. 27, 1964, Ser. No.406,928 Claims priority, application Germany, Nov. 16, 1963,

3 Claims. (Cl 260294.8)

The present invention relates to new pyridyl-1,3,5- oxathiazolinoneswhich possess biocidal properties, as well as a process for theirproduction.

It is an object of the present invention to provide new agents havingbiocidal properties, especially fungicidal and fungistatic properties aswell as insecticidal, acaricidal and herbicidal properties.

It has now been found that the new 4-pyridyl-l,3,5- oxathiazolinones-(Z)of the formula so=o possess strong biocidal properties.

It has further been found that 4-pyridyl-l,3,5-oxathiazolinones-(Z) ofthe Formula I are obtained if pyridine-thiohydroxamic acids of theformula (II) NOH \N era (III) C 0 C12 l 21101 N As starting materialsfor the present process, oz, 5 and y-pyridine-thiohydroxamic acids maybe used. These three isomeric compounds are clearly characterised byFormula I.

Some of the pyridine thiohydroxamic acids needed as starting compoundsare known. Thus, pyridine-4-thiohydroxamic acid is obtained by reactionof dithioisonicotinic acid with hydroxylamine [Berichte, 87, 827(1954)]. They can be advantageously produced by chlorinating the knownpyridine 'aldoximes according to the usual processes and reacting thepyridine hydroxamic chlorides thus obtained with alkali metalhydrosulp-hides in a likewise known manner. The course of the reactionis represented for rat-pyridine aldoxime by the following scheme.

FPIC

(1) NaHS An example of the two-step production of the starting materialsis given in Example 1.

As diluents for the reaction according to the present invention theremay be mentioned water as well as organic solvents such as hydrocarbons,(benzine, benzene), chlorinated hydrocarbons (chloroform,chlorobenzenes), ethers (diethyl ether, dioxan, tetrahydrofuran),ketones (acetone, methyl ethyl ketone), carboxylic acid esters (ethylacetate), nitriles (acetonitrile). As solvents, however, excess amines,e.g., pyridine, can also be used.

As acid binding agents the normally used inorganic acid-binding agentssuch as alkali metal and alkaline earth metal hydroxides, alkali metaland alkaline earth metal carbonates, and tertiary amines, e.g. pyridine,may be used.

The reaction temperatures may be varied within a wide range. In general,the process is operated at temperatures of between 20 and C., preferablybetween -10 and +50 C.

The reaction can be performed without pressure or under pressure. Incarrying out the process according to the invention, one mol ofthiohydroxamic acid is reacted with one to three mols of phosgene. Theacidbinding agent is applied in at least the twofold molecular amountcalculated on the thiohydroxamic acid used, but more advantageously, ina twofold molecular amount calculated on the phosgene used.

The compounds obtained according to the invention possess a very widerange of 'biocidal properties. They are fungicidally and fungistaticallyactive and can be used as leaf fungicides, e.g., against Phytophthorainfestans, Alternaia solani and types of genuine mildew. They are,however, also suitable as soil fungicides, e.g., against Tilletiatritici, Corticium rolfsii, Verticillium alboatrwm, Thielaviopsisbasicola, Fusarium culmorum, and Fusarium oxysporum. They canfurthermore also be used as insecticides, e.g., against flies, and asacaricides, e.g., against spider mites (T etranychus telarius). Thesubstances have moreover herbicidal properties and can therefore be usedas selective weed-control agents.

Their application as fungicides in the hygiene sector is also possible,e.g., against Trichophyton gypseum mentagroplzytes, Candida albicans,Penicillium commune, and Saccharomyces cerevisiae.

The compounds of the invention can be applied as such or in the form ofthe usual formulations, such as emulsifiable concentrates, spraypowders, pastes, soluble powders, dusting agents and granulates. Theseare produced in known manner (of. Agricultural Chemicals,

March 1960, pages 3538). The most important assistants are for thispurpose: solvents, such as aromatics (e.g., Xylene), chlorinatedaromatics (e.g., chlorobenzene), paraffins (e.g., mineral oilfractions), alcohols (e.g., methanol), amines (e.g., ethanolamine), andalso water; carriers, such as natural ground stone (e.g., kaolins,chalk) and synthetic ground stone (e.g., highly dispersed silicic acid);emulsifiers such as non-ionic and anionic emulsifiers (e.g.polyoxyethylene fatty acid esters, alkyl sulphonates), and dispersingagents such as lignin.

The active agents according to the invention can be present in theformulations in admixture with other known active agents, such asbacterides, fungicides, or insecticides.

The active compounds, their concentrations and the results obtained canbe seen from the following table:

TAB LE.PO ST-EME RGENOE-TESI Active agent Active agent concentrationMillet Rape Cotton Wheat Mustard Tomato Beans Oats in percent4-a-pyridyl-1,3,5-oxathiazolinone-(2) 0.2 5 5 I 4-5 2 5 i 3 l 4-5 V Theformulations contain in general from 0.1 to 95%, preferably from 0.5 to90%, by weight of active agent. Example test The substances of thepresent invention as well as their formulations are applied inconventional manner, e.g. by scattering, spraying, atomising orspreading.

Example A.Agar plate test (test for fangitoxic efiectiveness and breadthof the activity spectrum) tures are placed on it in small discs of 5 mm.diameter.

The petri dishes are incubated for 3 days at 20 C.

After this time, the inhibiting action of the active compound on themycelium growth is determined in different categories taking intoaccount the untreated control. 0 means that no mycelium growth occurred,either on the treated substrate or on the inoculum, the symbol meansthat mycelium growth occurred only on the inoculum,

Culture medium for Aspergillus niger: Beer agar. Culture medium forColi: Glucose bouillon.

One part by Weight of active agent is taken up in 5 parts acetone anddiluted with 95 parts by weight of water. From this preparation ofactive agent, in a test series of six test tubes, such quantities areadded to the above-mentioned culture medium liquified by heating thatthe resulting concentrations of active agent therein are 1:4000 to1120,000. After solidification, the culture medium is inoculated withthe test fungus.

After seven days incubation, the growth of the test fungus is examinedmicroscopically and the concentration determined in the whole series atwhich complete inhibition of the fungus has just occurred. If theconcentration of the active agent in the culture medium is, e.g. 121000the value 1000 represents the reciprocal inhibition value of thelimiting concentration.

From the following tables the test fungi and the reciprocal inhibitionvalues of the limiting concentrations are apparent.

TABLE.INHIBITIO N-TEST without spreading to the treated substrate, andthe symbol Reciprocal means that mycelium growth from the inoculum hasActive flu Test us hib t on value spread to the treated substrate,similarly to the spreading to the untreated substrate of the control.

h active Q E PP thelr concentratwns, the rest4-a-pyridyl-1,3,fi-oxathiazoli- {Aspergillusniger 12, 000 fungi and themhibltron effects achieved can be seen r on C011 12, 000 from thefollowing table: 50

TABLE.AGAR PLATE TEST Concentration g g g E g S E Active Agent ofActiveagent 5 E g g 5 g E g g E g g,, in Substrate gr. e g g S 3 5,; 6 .E a..E'E inp.p.m. ga 25 as $5 ea si s a as E g: n gas 8 e g2 g3.

4-a-pyridyl-1,3,5-oxathiazo1in0ne-(2) llllg l l I- ExampleB.P0st-emergence test Example D.Tetranychus test Solvent: 10 parts byweight; acetone Solvent: 10 parts by weight acetone. Emulsifier: 5 partsby weight; alkyl aryl polyglycol ether Emuls1fier: 5 parts by weightalkyl aryl polyglycol ether.

To produce a suitable preparation of active compound, To produce asuitable preparation of active compound, 1 part by weight of activecompound is mixed with the 1 part by weight of the active compound ismixed with stated amount of solvent, the stated amount of emulsifier thestated amount of solvent containing the stated amount is added and theconcentrate is then diluted with water to of emulsifier and theconcentrate so obtained is diluted the desired concentration. wlth waterto the desired concentration.

Bush beans (Phaseolus vulgaris), which have a height of approximately10-30 cm., are sprayed with the preparation of the active compound untildripping Wet. The bush beans are heavily infested with spider mites (Tetranychus telarius) in all stages of development.

After specified periods of time, the eifectiveness of the preparation ofactive compound is determined by counting the dead mites. The degree ofdestruction thus obtained is expressed as a percentage: 100% means thatall the spider mites are killed whereas means none are killed.

The active compounds, their concentrations, the evaluation times and theresults obtained can be seen from the following table:

TAB LE.PLANT-DAMA GIN G MITES Active agent Percent Active agentconcentration killed after in percent 48 hrs.4-a-pyridyl-1,3,5-oxathiazolinone- (2) a. 0.2 100 The following examplesare given for the purpose of illustrating the invention.

Example 1 Customary microbe culture media are treated with the graduatedamounts of each active agent and, after inoculation with germs or sporesof the stated microorganisms kept in an incubator for a prolonged periodof time under optimum growth conditions. The limiting concentration isthen determined, at which the microorganism is still completelyinhibited in its growth.

4-a-pyridyl-1,3,5-oxathiazolinone-(2) still inhibits the growth of thefollowing fungi to 100% extent at the following concentrations:

Trichophyton gypseum Candida Penicillium Saccharpmyces mentagrophytesalbicans commune ceremstae 5-10 v/ml- 50 1 l -20 'y/ l 50-100 'r/ml.

Example 2 in 500 cm. methanol saturated with hydrogen sulphide. Stirringis continued for a half hour with ice-cooling, for one hour at roomtemperature, and for one hour at 30- 35 C., followed by cooling to roomtemperature and filtering off the precipitated sodium chloride withsuction. The filtrate is almost completely evaporated in vacuum, theresidue is dissolved in 250 cm. of water. On acidifying,pyridine-2-thiohydroxamic acid separates. It is filtered off withsuction and freed from associated amounts of sulphur by dissolving it ina dilute caustic sodium solu tion, filtering and renewed precipitatingwith acid.

Yield: 37 g., M.P. C. (alcohol).

37 grams pyridine-2-thiohydroxamic acid are dissolved in a solution of29 g. sodium hydroxide in 250 cm. water. Into this solution phosgene isintroduced, with stirring and cooling to 5-10" C., and with thesimultaneous dropwise addition of a solution of a further 20 g. sodiumhydroxide in 100 cm. Water, until the mixture reacts neutral. Theprecipitated crystals are filtered off with suction, washed with water,dried and purified by dissolving in benzene and precipitating withligroin.

Yield: 27 g. 4-a-pyridy1-1,3,5-oxathiazolinone-(2) M.P. 127 C.

Example 3 Pyridine-3-aldoxime is chlorinated as described in Example 2,and reacted With sodium hydrogen sulphide, wherebypyridine-3-thiohydroxamic acid of M.P. 104 C. is obtained. Its reactionwith phosgene leads, as in Example 1, to4-,B-pyridyl-l,3,5-oxa-thiazolinone-(2) of M.P. 98 C. (benzine).

- Example 4 Pyridine-4-aldoxime is chlorinated as described in Example2, and reacted with sodium hydrogen sulphide, wherebypyridine-4-thiohydroxamic acid of M.P. C. is obtained. Its reaction withphosgene, as in Example 1, leads to 4-'-pyridyl-1,3,5-oxathiazolinone-(2) of M.P. 106 C. (benzene/ligroin).

We claim:

1. A 4-pyridyl-1,3,S-oxathiazolinone-(2) of the formula 2.4-a-pyridyl-1,3,5-oxathiazolinone-(2).

3. A process for the production of a 4-pyridyl-l,3,5- oxathiazolinonewhich comprises reacting a pyridine thiohydroxamic acid in the presenceof an acid-binding agent at a temperature between -20 and +l50 C. withphos gene and recovering the resulting product.

No references cited.

WALTER A. MODANCE, Primary Examiner.

ALAN L. ROTMAN, Assistant Examiner.

1. A 4-PYRIDYL-1,3,5-OXATHIAZOLINONE-(2) OF THE FORMULA